Back

Targeting Scavenger Receptor Type B-1 (SR-B1) and Cholesterol Inhibits Entry of SARS-CoV-2 Pseudovirus in Cell Culture

Henrich, S. E.; McMahon, K. M.; Palacio, N.; Bhalla, P.; Penaloza-MacMaster, P.; Thaxton, C. S.

2020-12-14 microbiology
10.1101/2020.12.14.420133 bioRxiv
Show abstract

The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China in late 2019 and has now caused a global pandemic. The disease caused by SARS-CoV-2 is known as COVID-19. To date, few treatments for COVID-19 have proven effective, and the current standard of care is primarily supportive. As a result, novel therapeutic strategies are in high demand. Viral entry into target cells is frequently sensitive to cell membrane lipid composition and membrane organization. Evidence suggests that cell entry of SARS-CoV-2 is most efficient when the target cell plasma membrane is replete with cholesterol; and recent data implicate cholesterol flux through the high-affinity receptor for cholesterol-rich high-density lipoprotein (HDL), called scavenger receptor type B-1 (SR-B1), as critical for SARS-CoV-2 entry. Here, we demonstrate that a cholesterol-poor synthetic biologic high-density lipoprotein (HDL NP) targets SR-B1 and inhibits cell entry of a SARS-CoV-2 spike protein pseudovirus. Human cells expressing SR-B1 are susceptible to SARS-CoV-2 infection, and viral entry can be inhibited by 50-80% using HDL NPs in an SR-B1-dependent manner. These results indicate that HDL NP targeting of SR-B1 is a powerful potential therapy to combat COVID-19 and other viral diseases.

Matching journals

The top 18 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.